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UNITED STATES DEPARTMENT OF AGRICULTURE 
BULLETIN No. 405 

Joint Contribution from the Bureau of Plant Industry. WM. A. TAYLOR, Chief, 
and the Bureau of Animal Industry, A. D. MELVIN, Chief 



Washington, D. C. 



PROFESSIONAL PAPER 



December 5, 1916 



LUPINES AS POISONOUS PLANTS 



By 

C. D. MARSH and A. B. CLAWSON, Physiologists, Drug-Plant 

and Poisonous-Plant Investigations, Bureau of Plant Industry, 

and HADLEIGH MARSH, Veterinary Inspector, 

Bureau of Animal Industry 



CONTENTS 



Part I.— Introduction . . . 
Part II.— Experimental Work 



Pago 
1 



Page 



Part ni.— Discussion and General Con- 

clnsiona 

Literature Cited 




WASHINGTON 
GOVERNMENT PRINTING OFFICE 

i9ie 



Monograph 



D. Of D. 

DEC £3 me 




Washington, D. C. 



PROFESSIONAL PAPER 



December 5, 1916 



LUPINES AS POISONOUS PLANTS. 

By C. D^Marsh aiul A. B. Clawson, Phijaiologisls, Drmj-Planl and Poisonous-Plant 
Investigations, Bureau of Plant Industry, and Hadleigh Marsh, Veterinary In- 
spector, Bureau of Animal Industry. 



Part I.— Introduction 

Summary of knowledge of lupines as 
poisonous plants 

Distribution of lupines 

Common names of lupines 

Alkaloids of lupines 

Ictrogen 

Part 11.— Experimental work 

Pharmacological investigations by Soll- 
mann 

Field experiments with lupines 

Laboratory experiments with extracts 

of lupine seed upon mice 

Part III.— Discussion and general con- 
clusions 

Failure to poison sheep in 1910, 1911, and 
1912 

Lupine not a cumulative poison 



Page- 
Part III.— Discussion, etc.— Continued. 

Toxicity of dillerent siwcies of lupine 30 

Toxicity of lupine leaves for sheep 30 

Toxicity of lupine seed for sheep 31 

Toxicity of lupine pods for sheep 32 

Toxicity of lupine fruit for sheep 32 

Symptoms 33 

Pathology 36 

Comparison of " lupinosis " and poisoning 

of sheep by American lupines 36 

Remedies 38 

Range conditions under which sheep are 

poisoned 39 

Treatment of range animals to avoid 

poisoning 41 

Summary -12 

Literature cited 43 



PART I.— INTRODUCTION. 
SUMMARY OF KNOWLEDGE OF LUPINES AS POISONOUS PLANTS. 

EARLY HISTORY AND LATER STUDIES. 

The lupines have been known from very ancient times, and are 
mentioned by many authors, e. g., Theophrastus, Marcus Fortius Cato 
Censorius, and Pliny. The last-named author (ed. 1856, pp. 49-50, 
452-453)^ treats of the lupine at length, especially with reference to 
its use as a green manure. Several species have been used as culti- 
vated crops in Europe, more especially for the reclamation of sandy 
soils. It has been used also as a fodder crop, and the seeds ground 

Note.— This paper will be or special interest to the stockmen of the West. 
1 Bibliographic citations in parentheses refer to " Literature cited," p. 43, 
52191°— Bull. 40&-16 1 



^ 



i.^^^ 



2 BULLETIN 405, U. S, DEPARTMENT OF AGRICULTURE. ^j^ \^ 

into meal have been used both for domestic animals and as food for 
man. In Germany the land utUized for lupine, according to the 
latest available statistics, is 346,753.3 hectares; on 200,000 hectares 
of this amount it is cultivated as a green manure. The poorer people 
among the Greeks and Romans and the Cynic philosophers made 
use of lupine meal in bread. The bitter principle was recognized not 
only as disagreeable, but as injurious, and the seed was especially 
prepared in order to get rid of this property. Among the Greeks the 
seeds were cooked until soft, to remove the outer skin, then placed in 
sacks in shallow places on the seashore to wash out the bitter prin- 
ciple. Afterwards the seeds were dried, ground in a hand mUl, and 
baked into a poor bread. Only the poorest people used this meal 
unmixed, but others mixed it with other kinds of meal, making a 
more digestible flour. (Landerer, 1852.) Because the lupines were 
planted in Maina and there used for food, the people in that region 
were known as ''Lupinophagi." Lupine meal was also used by the 
ancient Egyptians, and is stUl used in Andalusia, Corsica, and Pied- 
mont. (Cornevin, 1893, p. 314.) In modern times lupine meal, after 
a process of "Entbitterung," has been used to some extent as food 
for animals. 

As a medicine, lupine seeds have been used since ancient times. 
Pliny (ed. 1856, p. 452-453) enumerates 35 different uses. The 
main uses, however, seem to have been as a cathartic and as a vermi- 
fuge. For the latter it was used as an external application as well 
as internally. 

BeUini (1876) reports in detail cases of poisoning in man from 
using a decoction of lupine as an enema. He states that Averrhocs 
and Hofman pointed out the poisonous properties of the plants, and 
that Paullus, 1708, reports a case of poisoning of a boy by an enema. 
The reference to Averrhoes and Hofman could not be verified, as 
apparently they only mentioned the plants as a vermifuge. The 
symptoms mentioned by Bellini are dyspnoea, defective sight, dilated 
pupils, and stupor. These symptoms, as will be seen later, compare 
fairly well with those of poisoning by the lupine alkaloids. 

Isolated cases of poisoning by lupmes were noted as early as 1860, 
but it was in 1872 and the foUowmg years that heavy losses of sheep 
occurred in northern Germany. Wliile there is evidence that some 
animals are poisoned by the alkaloids, most of the cases, and prac- 
tically all of the losses, have been from the use of lupine hay and are 
caused, as will be seen later, by ictrogen. The occasional poisonmg 
of cattle and horses reported in Europe appears to have been from 
the use of the seed and is alkaloidal poisoning. Sheep are also 
poisoned in this way, but the great losses which have stimulated the 
extensive investigation of the subject have been by ictrogenic poison- 
ing of sheep. 



LUPINES AS POISONOUS PLANTS. 3 

In America tlie first published report of losses of sheep is l)y 
Chesnut (1899, p. 404-405), and this report with the papers of 
Wilcox (1899), Chesnut and Wilcox (1901, p. 100-110), and Slade 
(1903), comprise all that has been pubhslied up to the present time. 
Other authors have mentioned the subject, but their material is 
all taken from tlie reports of Wilcox, and Cliesnut and Wilcox. 
The first general account of lupuio poisoning in America is by 
Wilcox (1899). A much more extended account is given by 
Chesnut and Wilcox (1901, p. 100-110), with details of cases and 
symptoms. Wilcox notes that mature plants are the more poison- 
ous, and Chesnut and Wilcox definitely state that the toxic principle 
is mainly in the pods and seeds and that lupine hay should be cut 
after the seeds are shed. Both WUcox, and Chesnut and Wilcox 
apparently consider the poisoning of sheep in America as similar to 
the disease called "lupinosis" in Germany, although Chesnut and 
Wilcox (1901, p. 109) state that the ''chronic form of the disease" 
has not been recognized in America. Sollmann, hi an impubhshed 
report of a laboratory study of American lupmes, a report made 
under the direction of the Bureau of Plant Industry, which wUl be 
discussed more fully later, states that he failed to find evidence of 
the presence of ictrogen and gives details of the symptoms produced 
by the alkaloidal substances extracted by him. His work was not 
connected with field investigations, but the results, viewed in the 
fight of present knowledge, clearly indicate the probability that the 
field cases of poisonmg by lupme in America are not cases of 
"lupinosis" m the sense in which the temi is used in Europe, but are 
the result of alkaloidal poisonmg. The field mvestigations reported 
in this paper establish without a doubt the fact that, so far as ob- 
served, all cases of poisonuig of range slieep by lupines must be con- 
sidered as due to the alkaloids and not to ictrogen. These field 
investigations are in entire harmony with tlie preliminary laboratory 
study by Dr. SoUmann, althougli carried on in an independent way 
without reference to the precedmg results obtained in the laboratory. 

ANIMALS POISONED BY LUPINES. 

Wliile the losses of domestic animals have been mainly of sheep, 
other animals also are poisoned — horses, cattle, goats, swine, and 
fallow deer — and laboratory experiments on small animals indicate 
that none are immune to the effects of the toxic substances. 

Wilcox (1899) states that in Montana a few horses have been 
poisoned, and Chesnut and Wilcox (1901 p. 100-110) give specific 
instances. Poisoning of horses on the range or in pastures is not 
common, but is known to occur. Dammann (1902) states that 
cattle are affected by the alkaloid, and cases of the poisoning of 
cattle on the range have been reported in America, although the 
cases are not very weU authenticated. 



4 BULLETIN 405, U. S. DEPAKTMENT OF AGRICULTURE. 

LOSSES FROM LUPINES. 

The losses from "lupinosis" in Europe have in some years been 
very great. In 1880, in Pomerania the loss of sheep was 5.89 per 
cent (Comevm, 1893, p. 316). It is stated that in some herds in 
northern Germany the loss was as great as one-half to three-fourths 
of the total number. 

The known losses in America are very heavy. Chesnut and 
Wilcox (1901, p. 106) teU of one case, among others, in which out 
of 2,000 sheep trailed over a region covered with a large quantity of 
lupine 1,000 were sick and 700 died. In another case 1,150 died out 
of 2,500 (p. 104). Losses of several hundred are not at all uncommon, 
and occasionally the deaths may be nearly 50 per cent of the whole 
number. More complete knowledge of the losses has been obtained 
in Montana than in any other State, because Montana has been under 
close observation for many years, and it is very possible that this 
State suffers more than others, but more or less similar conditions 
are found in other western States m which the mountain regions are 
used for sheep grazing. It is probable that the lupines rank as a 
close second to Zygadenus in causing losses of sheep. 

DISTRIBUTION OF LUPINES. 

While lupines are found m the eastern United States rather spar- 
ingly, and are there represented by only three species, in the Western 
States there is a large number of species, and these frequently grow 
in large masses, so that sometimes they are cut for hay. They form 
an important factor in the number of forage plants. Horses seem 
to be especially fond of them and wiU sometimes eat the green plants 
with great greediness. 

Of the species of lupines in America, only a few have been used 
in this investigation. One of these, Lupinus sericeus, is illustrated in 
figure 1. A thorough systematic study of the genus is in progress 
by the Bureau of Plant Industry, and further work is being prose- 
cuted for future publication, dealing with the characteristics of the 
different species from the standpoint of chemistry and pharmacology, 
as well as from the standpoint of field experimentation. 

COMMON NAMES OF LUPINES. 

The lupines are known under a large number of common names. 
Among these are sundial, old-maid's bonnets, Quaker's bonnets, 
Indian beans, wild beans, blue pea, and blue bean. In some sections 
the name loco is used, but this is generally by those who do not 
know the true locoes. 



LUPINES AS POISONOUS PLANTS. 5 

ALKALOIDS OF LUPINES. 

No investigations of the alkaloids of iVinerican lupines have been 
published, but the European lupines have been the subject of ex- 




FiG. 1.— Lupine (Lupinus sericeits). 



tended study, and the literature, especially of the chemistry of the 
alkaloids, is very large. 

Cassola (1834) attempted to isolate the alkaloid of Lupinus alhus, 
but probably did not obtain the pure alkaloid. Landerer (1852) 



6 BtTLLETTlSr 405, U. S. DEPARTMENT OF AGRTCTTLTtTKE. 

obtained a substance that showed a begmnmg of crystallization, 
which he called lupmin. Beyer (1871), found an alkaloid in lupine 
from a study of Lujnnus luteus. Baumert issued a series of papers 
from 1881 to 1889. Baumert (1886) summarizes the knowledge to 
date and announces definitely the presence of two alkaloids in Lujnnus 
luteus, lupmin (C21H40N2O2), and lupinidin (CgHigN). Schmidt (1897), 
Davis (1897), Callsen (1899), Schmidt (1904), and Bergh (1904) 
summarize and bring the subject to date with extensive additions 
to the detailed chemistry of the alkaloids. Schmidt (1897) states 
the alkaloids as lupinm (C21H40N2O2), lupmin (CgH^jN), ''dextro- 
rotatory-lupanm " (C15H24N2O); and inactive lupanin (CgoH^gN^O,) . 
These are found in the lupines examined, as follows: 

Lupinus angustifolius dextrorotatory-lupanin. 

Lupinusalbus rdextrorotatory-lupanin. 

Unactive lupanin. 

Lupinus luteus {IT^!"^; 

Uupinidm. 

Lupinus niger flupinin. 

Uupinidin. 

Lupinus perennis dextrorotatory-lupanin. 

Lupinidin is identical with spartein C15H26N2 (Muenk, 1914, p. 394). 

CaUsen (1899) gives an extended account of the chemistry of the 
alkaloids of Lupinus angustifolius and L. perennis. Willstatter and 
Fourneau (1902) give experimental evidence that the formula of 
lupinin is C10H19ON. Schmidt (1904) and Bergh (1904) in extended 
papers discuss further the alkaloids and state that another alkaloid 
is found in Lupinus perennis, oxylupanin (C15H24N2O2). 

Liebscher (1880), Lowenthal (1888), and Eaimondi (1891) give 
details of the pharmacology of the lupine alkaloids. The action of 
all is practically the same but differs quantitatively. Liebscher 
states tliat lupinidin is 10 times as active as lupinin. There is a 
direct paralysis of the medulla and cord, the respiratory center being 
first paralyzed, and then the vasomotor. This is accompanied by 
weakening of the heart. There is a fall in blood pressure, a slowing 
of the pulse, and dilation of the pupils. Death is produced by 
asphyxia, with which are associated convulsions. 

There is no cm-are action. The dose required to produce any 
symptoms is ordinarily fatal. The alkaloids are less poisonous for 
mammals than for cold-blooded animals. Small repeated doses pro- 
duce no effect, nor do they estabhsb a condition of tolerance. 

ICTROGEN. 

Early in the investigation of the poisoning of domestic animals in 
northern Europe by lupines, causing the disease which came to be 
known as "lupinosis," it was observed that these were not cases of 
poisoning by the recognized alkaloids of the lupines. Lupinosis has 



LUPINES AS POISONOUS PLANTS. 7 

a definite line of symptoms distinctly different from those produced by 
the alkaloids, especially characteristic being a hepatitis, which pro- 
duces a jaundice exhibited in the conjunctiva and visible mucous 
membranes of the Uving animal. Kiibn (1880), Roloff, (1883), 
Arnold and Lemke (1881), as well as others, found that the intoxica- 
tion known as lupinosis could not be produced by alcoholic extracts, 
but was produced by the marc of the seeds; if the poisoning were 
alkaloidal, tlie reverse would be the case. Dammann (1902, p. 343) 
states that the plant often becomes more toxic on keeping. More- 
over, while the alkaloids are always present the ingredient producing 
lupinosis is inconstant. The plants raised on some fields always 
produce poisoning, wliile on others they are harndess (Raimondi, 
1891). It was. found (Dammann, 1902, p. 342) that the substance 
producing the disease is insoluble in alcohol, ether, glycerine, and fatty 
oils, and is soluble with difficulty in water. It is not readily destroyed 
by dry heat, but steam under pressure makes it harmless. This 
h\T)othetical substance was called ictrogen by Kiihn (1880) and 
lupinotoxin by Arnold and Schneidemiihl (1883). It has only been 
recognized by its physiological action. 

Ictrogen is not considered to be a product of the metabolism of the 
lupine, but to be the result of the growth of microorganisms upon the 
plants. Tliis explanation is not based, however, upon any experi- 
mental evidence, but is reached by a process of eUmination of other 
possible theories. This is the theory advanced by Dammann (1902, 
p. 341-343). Other theories of the cause of lupinosis have been 
advanced. For example, Ziirn (1879) propounded a theory that the 
disease is produced by microorganisms in or on the lupine leaves; in 
other words, that lupines do not cause the disease, but simply serve 
as a carrier. This theory has not been taken very seriously by others, 
while the theory that the disease is produced by ictrogen and that this 
substance is produced through tlie action of some unknown micro- 
organisms upon the lupines is quite generiilly accepted as the most 
probal)lo explanation. 

PART II.— EXPERIMENTAL WORK. 

PHARMACOLOGICAL INVESTIGATION BY SOLLMANN. 

SCOPE OF THE WORK. 

A series of experiments upon Montana lupines, identified as 
Lupinus sericeus, L. leucopJiyllus, and L. cyaneus, was conducted by 
Dr. Torald Sollmann, under the general direction of V. K. Chesnut, 
then in charge of the work on poisonous plants in the United States 
Department of Agriculture, and following is a report of the results. 

Eighteen animals, rabbits and guinea pigs, were fed upon pods 
and seeds \\Hth no results, none of them eating enough to produce 
toxic effects. 



8 BULLETIN 405, U. S. DEPARTMENT OF AGEICULTUEE. 

Extractions were made of the seeds and pods, and impure alkaloids 
were obtained. The experience in this work leads to the suggestion 
of the following method of extraction: 

Moisten the powdered drug with alcohol containing 1 per cent of HCl; pack in 
percolator; macerate with alcohol; percolate with alcohol until the percolate gives 
only small turbidity with Mayer's reagent. Mix the percolate with sand and evaporate 
the alcohol. Treat the residue repeatedly with warm water, until it gives off only a 
slight reaction with Mayer's reagent. To the united filtrate add Mayer's reagent to 
complete precipitation. Wash the precipitate, suspend it in a little water, and decom- 
pose with HjS; filter. 

Evaporate the filtrate to a small voliune, add an excess of Ca(0H)2, filter, exhaust 
the precipitate and filtrate separately with ether, as quickly as possible, neglecting 
the last traces. Evaporate the ether. Treat the residue with absolute alcohol acidu- 
lated with H2SO4. Let stand 24 hours. The precipitate will contain the lupinidin, 
the filtrate the other lupine alkaloids. These will require further purification. 

CHARACTERS OF THE ALKALOmS. 

Physical characters. — The physical effects of the aklaloids make it 
likely that they are similar to those occurring in the European 
species. Several of these characters were observed in the course of 
the isolation of the alkaloids. 

The (impure) alkaloids were obtained as brown oily liquids of a 
strongly alkaline reaction and a strongly bitter taste. They were 
easily soluble in water and in alkalies. They were slightly soluble 
in petroleum ether. No crystals were obtained. During their sepa- 
ration a strong odor resembling conin, characteristic of lupinidin, 
was perceptible, especially when strong soda was added. The 
isolated alkaloids were almost odorless, but again developed the odor 
very strongly when 10 per cent soda was added. 

Chemical characters. — Strongly heated, they boiled and evolved 
dense, white fumes. Strong sulphuric acid, cold or heated, alone or 
with formaldehyde or bichromate, gave only browning. Strong 
nitric acid also gave no characteristic reactions. 

Precipitation reactions. — -The alcoholic solution gave partial pre- 
cipitation with sulphuric acid. The dilute neutral aqueous solutions 
of the chlorid or sulphate behaved as follows : 

NaOH (1 per cent): Slight precipitate. 

NaOH (strong): Precipitate, partly soluble n excess of the soda. 

(NH4)0H: No precipitate. 

NaaCOj: No precipitate. 

Mercuric chlorid: Amorphous precipitate, easily soluble in excess of HCl. The 
precipitate was incomplete, giving further precipitate with Mayer's reagent, and also 
the lupinidin test with alcoholic sulphuric acid. 

Picric acid: Fair amorphous precipitate. 

Tannin: Precipitate, soluble in excess. 

lodin in KI : Good amorphous precipitate. 

Pot. f errocyanid : No precipitate. 

Pot. bichromate: No precipitate. 



LUPINES AS POISONOUS PLANTS. 9 

Nature of the alkaloids. — The alkaloids were not obtained sufficiently 
pure to make definite characterizations possible. Their close agree- 
ment with those obtained from the European species in physiological 
action and fatal dose make it very probable that they are closely 
related, if not identical. Lupinidin was fairly well identified by the 
conin odor, by the insolubility of the double clilorid formed y\\ih. mer- 
cury, and by the insolubility of the acid sulphate in absolute alcohol. 
The precipitation by these reagents was not complete, so that there 
must be other alkaloids present, presumal)ly lupinin and lupanin. 
This portion of the work needs further elaboration. 

The yield of crude alkaloids in the extraction was as follows: 

Specimen IV: Lupinus sericeiui, parasitized pods, 0.02 per cent from alkaline ex- 
tract; 0.133 per cent from watery extract. 
Specimen V: Lupinus cyaneus, seed, 2.462 per cent. 

Gerhard found from 0.5 to 1.2 per cent in the European lupines. 

TOXICITY OF THE EXTRACTS. 

The various extracts, prepared as described, were admmistered to 
rabbits and guinea pigs, by mouth, stomach tube, and hypodermi- 
cally. The symptoms were practically identical, and will be described 
later. It was found : 

(a) That the toxic principles must be alkaloidal rather than ictrogenic. 

(6) That the fatal dose of the drug (as extracts) to ral)l)its by stomach, in the case of 
the seeds of Lupinus sericeus and L. leucophyllus, vva-s between 30 and 50 grams per 
kilogram, with the seeds of L. cyaneus between 70 and 100 grams per kilogram, and 
with empty pods of L. seria'us and L. cyaneus over 100 grams per kilogram. 

(c) That the fatal dose of the crude alkaloids (in the purest lomi in which they were 
used, from Specimen V) lies, for rabbits, gastric administration, between 1.2 and 2.4 
grams per kilogram; for rabbits, hypodeniiic admirdstration, between 0.123 antl 0.246 
grams per kilogram (agrees with Lowenthal's (1888) figures for lupinitlin and lupanin, 
viz, 0.2 and 0.4); for guinea pigs, hypodermic administration, between 0.052 and 0.1 
gram per kilogram. 

{d) That the alkaloids are five to ten times as toxic for rabbits when given hypo- 
dermically as when given by the stomach tube. 

(c) That guinea pigs are about twice as susceptible to the poison, when given liypo- 
dermically, as rabbits are. 

(/) That repeated administration of the poison to animals did not increase their 
8U.sceptibility, as is shown by the fact that rather prolonged feeding was not fatal, 
and that no tolerance is produced in this manner, as is shown by rabbits 77 and 78 A. 
The animals in either case, after having been injected repeatedly, died from the last 
dose, although these doses were not very greatly above the fatal limit. 

SYMPTOMS OF LUPINE POISOMNG. 

It will be iisefid to describe the typical course, which occurs with 
only minor variations when any of the extracts are administered. 
The symptoms set in with a general depression. The animal is 
very quiet, sits flat with ears laid back; the respiration is rapid, 
labored, and irregular. The temperature is not altered in a constant 
manner. After a time it is noted that the animal, while apathetic 
52191°— Bull. 405—16 2 



10 BULLETIN 405, U. S. DEPARTMENT OF AGRICULTURE. 

if left alone, is quite excitable when disturbed. The reflexes are 
heightened. The movements are brusque and exaggerated. The 
depression gradually deepens; the animal partly loses control of its 
hind legs, so that these tend to drag. Often the animal Hes on its 
belly, the head on the floor and legs spread out. It is still able to 
walk. It soon loses this ability and sits or lies stiU. When disturbed, 
it reacts with shivering, and becomes more and more convulsive. 
Stimulation now produces more or less violent spasms, the first spasm 
being strongly tetanic. The animal may assume the strychnin posi- 
tion, with legs stretched out, and back arched in; or it may rise on 
its feet, the back arched upward. The spasm soon becomes clonic 
and incoordinated, the animal pawing the air in an aimless manner. 
This is followed by relaxation, and the animal remains quiet unless 
disturbed, which disturbance would cause another spasm. After a 
time the convulsions occur spontaneously. In milder cases there 
may be no general convulsions, but twitching of isolated muscles— 
of the face, ears, neck, back, and extremities. The head may swing 
in a rhythmical pendulum movement. The respiration during this 
convulsive paralytic condition is slow, shallow, and irregular. The 
pupils are variable, but need not be dilated (which speaks against 
the view that they are asphyxial; the mucous membranes are also a 
bright pink). Many animals urinate copiously. The animals may 
remain on the abdomen or recover a sitting postute for some time 
after the onset of the convulsions, but after a time they fall on the 
side. The respiration becomes gasping. Asphyxial convulsions set 
n, and the respiration stops from half a minute to 1 minute before 
the heart. 

The depressant and convulsive symptoms agree with those de- 
scribed by Lowenthal (1888), Gemma (1882), and Raimondi (1891) 
for European lupine alkaloids. 

It is not possible to make any general statement as to the time 
required for the development of the different symptoms, since this 
is extremely variable. It is remarkable, however, that a consider- 
able time may elapse before any pronounced symptoms appear, 
and this even when the solutions are administered under the skin. 
It is to be noted that doses which are little below fatal produce only 
very slight symptoms. 

Recovery may occur from any stage and is usually so complete 
that the animal gains on its original weight. The intoxication leaves 
no post-mortem lesions, gross or microscopical. 

OPERATIVE EXPERIMENTS WITH LUPINE ALKALOIDS. 

The effects on blood pressure, respiration, etc., were studied on 
five dogs, anaesthetized with morphin and ether, and arranged for 
tracings. The alkaloidal extract of Specimen V (seeds of Lujnnus 



LUPINES AS POISONOUS PLANTS, 11 

cyaneus) was injected into the femoral vein, in progressively increas- 
ing doses. Tlie dose is calculated as grams of drug (not of alkaloid) 
per kilogram of body weight. Arranged by doses, the effects were 
briefly as follows : 

SMALL DOSES OP 0.1 TO 0.4 ORAM PER KG. 

Respiration : First quicker and deeper; then somewhat slowed; irregular, and shallow. 

Carotid blood pressure: Rise, fall, rise, normal. 

Heart : Rate somewhat quickened; strength somewhat diminished. 

TOXIC DOSE.S OF 0.5 TO 0.75 GRAM PER KG. 

Respiration: First quickened and deeper; then somewhat slowed, irregular, and 
shallow; may stop. 

(Carotid blood pressure: Rise, then great fall; effect of sciatic stimulation le.ssened. 

Heart: Rate first slowed, then quickened; when vagi were cut, slowed; strength, 
weakened. 

VERY LARGE DOSES OF 0.9 TO 6.25 GRAMS PER KG. 

Respiration: For a few moments deeper; then very shallow and stops. 
Carotid blood pressure: First slight rise, then great fall. 
Heart: Rate first slowed, then quickened, then stopped; strength weakened. 
Convulsions may occur from 1 gram up. 

DISCUSSION OF EFFECTS. 

Respiration. — The respiration shows a short stimulation (increase 
of rate and depth), followed by depression (slowed, irregular, shal- 
low); with the larger doses it stops before the heart. The action is 
probably on the centers, for it occurs after section of the vagi, and 
when stoppage has occurred it can not be revived by asphyxia, slap- 
ping, or stimulation of the sciatic, or injection of saline. No recovery 
occurs from even a just fatal dose after an hour of artificial respiration. 
The respiratory center is the first vital center to give out completely. 

Blood pressure. — This shows a short, moderate rise, followed by a 
more lasting fall, which is quite marked with the larger doses, even 
those which are not fatal. ^^Uthough tlie changes often coincide with 
respiratory changes, the two are not interdependent, for they may 
occur independently, and blood pressure changes occur even during 
artificial respiration and are not influenced by the latter. Whether the 
changes were central or peripheral was not investigated directly; but, 
from the fact that when vasomotor paralysis exists stimulation of the 
sciatic is sometmies efl'ective and sometimes ineffective when asphyxia 
is efl'ective, it is rendered very probable that the action is central. 
The vasomotor paralysis may precede, coincide, or follow that of 
respiration. It may be partial or so nearly complete that the pressure 
smks to some 20 millimeters with a good heart action. 

Tlie heart rate. — With toxic doses there is first slowing, then quick- 
ening; with minimal and maximal doses, there is usually quickenuig 
only. Tlie slowing and secondary quickening occur equally well 
when the vagi are divided ; they are therefore at least partly periph- 
eral. They are not always accompanied by changes in the strength 



12 BULLETIN 405, U. S. DEPARTMENT OF AGRICULTURE. 

of the heart, hence they are probably not muscular. Further, when 
the heart is quickened by large doses, electric stimulation of the 
vagus has but little effect. The drug may therefore be said first to 
stimulate and then depress the vagus end mechanism. It may have 
a similar action on the vagus center. 

Strength of the heart. — This is affected only by rather large doses, 
but it is then always depressed. Experiment 87 shows that the life 
may be kept up with a complete vasomotor paralysis, if the heart 
beats well. This tends to show that the stoppage of the heart, which 
forms the final cause of death, must be due to paralysis of its muscles. 
This is confirmed by the fact that it can not be revived by injection 
of normal saline. 

Convulsions. — Convulsions were observed in but two of the five 
cases. This may be due to the anaesthetic or to the difficulty of 
securing proper dosage. When observed, however, they preceded 
respiratory distress and were not connected with any change in 
blood pressure, so that it seems that they are produced by a direct 
central action. 

Slceletal muscle. — The existence of convulsions in the last stages, as 
well as the result of stimulation of peripheral and of the sciatic, show 
that muscle and nerve are not paralyzed. 

Cause of death. — The following vital functions are eventually 
paralyzed by the lupine: Respiratory center; vasomotor center; 
cardiac muscle; the last named being the last to become paralyzed 
and being the final cause of death. 

SUMMARY. 

The results of the investigations are in many respects incomplete 
and emphasize the need of a more exhaustive chemical and pharma- 
cological study of the American lupines. They have shown, how- 
ever, that these lupines contain alkaloids which are toxic or fatal if a 
sufficient ciuantity of the plant is consumed, but which are harmless 
if the consumption is below a certain limit. Up to this point the 
lupines may be a useful food if due precautions are observed that the 
limits are not surpassed. These alkaloids could also be largely 
removed by leaching with water. The ictrogen, which is especially 
feared in Europe, was not found in any of the American samples. It 
would be of great importance to determine whether this ictrogen is 
uniformly absent, for if it is not, much more stringent precautions 
would be necessary. 

CONCLUSIONS. 

1. Feeding with the lupines does not produce any symptoms in 
rabbits and guinea pigs, as a sufficient quantity is not taken in this 
manner. 

2. The injection of extracts, by stomach or skin, is fatal if suffi- 
ciently large doses are used. 



LUPINES AS POISONOUS PLANTS. 13 

3. No ictrogen was found in any of the six specimens, 

4. The toxic constituents are alkaloidal and seem to agree with 
those of the European species. 

5. These alkaloids produce a stimulation and then a paralysis of the 
following structures: The respiratory and vasomotor centers, some 
convulsive centers, the vagus end mechanism, and perhaps the 
vagus center. Large doses given intravenously paralyze the heart 
muscle. The convulsions do not appear to be purely asphyxial. 

6. Pronounced symptoms are seen only when almost fatal doses 
are given; smaller amounts do not produce any conspicuous effects. 
When death does not occur acutely, there are no late effects. Re- 
peated administration has no influence on the action. 

7. The cause of death is paralysis of respiration. Death occurs, 
with hypodermic administration, in 12 minutes to 2.^ hours; when 
given by stomach, in 10 minutes to 3^ hours. The symptoms set in 
only shortly before deatli. 

8. The fatal doses for rabbits by the stomach, figured for the 
original drugs, are as follows: For .the seed of Lupinus sericeus and 
L. leucophjllm, between 30 and 50 grams per kg.; for the seed of L. 
cyaneus, between 70 and 100 grams per kg.; for the hulls of L. cya- 
neus, and L. sericeus, over 100 grams per kg. 

9. The fatal dose of the crude alkaloid for rabbits, gastric admin- 
istration, lies between 1.2 and 2.4 grams per kg.; for rabbits, hypo- 
dermic administration, between 0.123 and 0.246 gram per kg.; for 
guinea pigs, hypodermic administration, between 0.062 and 0.1 gram 
per kg.; for dogs, intravenous administration, about 0.012 gram 
per kg. 

10. The fatal dose for rabbits is between 5 and 10 times as large 
when the alkaloids are given by the stomach as when given intrave- 
nously. Guinea pigs are more susceptible to the alkaloids than 
rabbits when the solutions are administered hypodermically. 

11. In the treatment of the poisoning, artificial respiration was 
found useless. Good results were obtained with potassium perman- 
ganate, diuretin, and tea. 

FIELD EXPERIMENTS WITH LUPINES. 

Field experiments with domestic animals have been carried on for 
six years — in 1909, 1910, and 1911 at Mount Carbon, Colo., and in 
1912, 1913, and 1914 at Greycliff, Mont. Two species, Lupinus 
cnmatus and L. myrianthus, were used at the Mount Carbon station. 
At Greycliff most of the work was done with two local species, i. 
leucopsis and L. argenteas, but two feedings were made with L. 
leucophyUus collected in Idaho in the Caribou National Forest. Not 
only were different species used, but feedings were made of different 
parts of the plants and also with the plants at different stages of 
growth. 



14 



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20 BULLETIN 405, U. S. DEPARTMENT OF AGRICULTURE. 

Inasmuch as nearly all the recorded losses are of sheep, most of 
the work was done with these animals, there being, all told, 141 
experimental cases. Two head of cattle were fed, and there were 
10 experiments with horses. Table 1 contains a summarized state- 
ment of the field experimental work. 

EXPERIMENTS WITH CATTLE. 

Two head of cattle, Nos. 108 and 620, were fed with lupine, but in 
neither case was there any result. Tliis should not be interpreted, 
however, as proving that cattle can not be poisoned by lupme; 
accounts have reached the Department of Agriculture of the poisonuig 
of cattle in the field under circumstances which make it seem very 
probable that lupine was the cause. However, it does not seem 
probable that the lupines cause any serious loss of cattle. 

EXPERIMENTS WITH HORSES. 

There were 10 experiments of feeding lupine to horses, 8 with Lu- 
pinus myrianthus and 2 with L. comatus. Horse No. 72, between 
September 22 and 26, 1909, ate, per 1,000 pounds of its weight, 77.2 
pounds of lupine, including leaves, stems, flowers, and fruit. The 
animal died, the marked symptoms being general depression and 
dullness, abdominal pain, twitching of the surface muscles, and high 
steppmg as he walked about. The animal was very much consti- 
pated and in the autopsy there was clear evidence of intestinal im- 
paction. At the time, because of the negative results obtained, it was 
thought probable that the intestinal impaction was the cause of 
death, but a review of the case, after more complete Ivnowledge of 
lupine poisoning, made it appear quite certain that this horse was a 
victim of lupine intoxication. 

The two feeding experiments with horse No. 124 were negative. 
With horse No. 78 there were five feeding experiments with Lupinus 
myrianthus — two in 1909, two in 1910, and one in 1911. In 1911 
there were also two experiments with this horse of feeding L. 
comatus. In four of the experiments with horse No. 78 there were 
distinct symptoms of illness, consisting of contractions of the surface 
muscles, intestinal disturbance, indicated in the main by constipa- 
tion but showing diarrhea m one case, dullness and depression, with a 
tendency to lift the fore feet unusually high when stepping about. 

The experiments with horses were sufficient to establish the fact 
that these animals may be poisoned by the lupines. No deductions, 
however, can be drawn as to the toxic dose, since the periods during 
which the feedings were continued were extremely variable. To estab- 
lish definitely the dosage for horses would require a large number of 
caref uUy conducted experiments comparable with those on sheep, and 
for such experiments there has been as yet no opportunity. 



LUPINES AS POISONOUS PLANTS. 21 

EXPERIMENTS WITH SHEEP. 

In the experimental work with sheep the attempt was made to 
have the animals, if possible, eat the plant. In experiments with 
seeds it was found that the extremely bitter taste led the sheep to 
avoid them, but when they were ground up and mLxed with bran 
the material was eaten quite readily. Wlien it was found difficult, in 
the case of corral animals, to get them to eat enough to produce 
any effect, drenchmg and forced feeding were used. In drenching, 
the sheep was placed on its haunches and the drench, which con- 
sisted of the plant material fmely ground and suspended in water, was 
given by a bottle. For the forced feeding the material was ground 
and given by means of a vetermarian's ballmg gun. The plant mate- 
rial fed m this maimer was placed a little at a time m the back part of 
the sheep's mouth. As soon as this was swallowed more was given, 
and the process continued until the desired quantity had been given 
to the animal. 

TYPICAL CASE OF SHEEP NO. 184. 

Sheep No. 184, a 2-year-old ewe weighing 62.5 pounds, was taken 
into the corrals on August 16, 1913, for feeding. On August 17, at 
8.45 p. m., she was given 200 grams of ungromid seed of Lupinus 
leucopsis, mixed with oats, corn, and wheat, which wtis equivalent to 
0.705 pound per 100 pounds of animal. During the day this was all 
eaten. 

On August 18, at 6.55 a. m., the sheep was foimd lying partly on 
one side with her head on the ground, as though in sleep, and trem- 
bling in the forelegs. When stimulated she attempted to get up, 
but was unable to raise her body from the ground. Through the 
struggle the respiration became more marked and heavy, the animal 
breathing much as though in a deep sleep. After the struggle the 
pulse was 174 and fairly strong. At 7. 10 a. m. the respiration was 36 
and the temperature 101° F. Plate I, figure 1, shows the condition 
of the animal as she appeared at 7.15 a. m. At 8 a. m. she lay with 
her head extended on the ground, in much the same position as at 
7.15. She raised her head for a few moments, then slowly dropped it 
with eyes half closed, as if in sleep. At 8.05 a. m. she held her head 
up, and apparently made an effort to walk. Her respiration was 36 
per minute, noisy, and deep. Her sides trembled as she breathed. 
The pulse was 122. At 8.50 a. m. she got upon her feet and stood sev- 
eral minutes, then leaned against the fence and sank dow^l again. At 
8.55 a. m. she stood with her legs bent at the knees as though in an 
effort to balance herself. Her respiration was 36 and of the same 
character as before. There was some frothing at the mouth. Her 
ears hung low. Plate I, figure 2, shows the attitude of the animal at 
8.57. At 10.30 a. m. she lay breathing as before and trembling. 
Her temperature was 103.3° F. At 10.35 a. m. she was raised upon 



22 BULLETIN 405, U. S. DEPARTMENT OF AGRICULTUEE. 

her feet and then tried to walk, but was unable to stand, and lay down 
again. At 10.47 a. m. she was unable to get her breath and went into 
a spasm, in which her legs straightened out very much as though she 
had been poisoned by stryclmin. At 10.48^ a. m. she was breathing 
again more naturally. She lay upon her side, trembhng violently, 
with her hind legs extended rigidly. At 10.50 a. m. she was quiet 
again. At this time she appeared to be a little bloated. At 10.52 
a. m. the muscles were rigidly contracted again, and the trembling 
became more violent; this was followed by a spasm, in which she had 
great difficulty in getting her breath. At 10.55 a. m. she quieted 
down again, and her respiration became more regular and deep. At 
10.56 a. m. another spasm came on. At 10.58 a. m. she was quiet 
again, with pulse 174, strong, and regular. At 11 a. m. another spasm 
came on, but the animal soon became quiet. At 11.08 a. m. the head 
was thrown back, the heart fluttered, respiration stopped, and at 
11.10 a. m. the animal was dead. For several minutes before death 
the heart action was weak, and just before death she was miable to 
get her breath. The muscles gradually relaxed, the head was drawn 
back, and the heart stopped. 

An autopsy was made upon the animal immediately, but very little 
abnormal was fomid. The heart stopped in systole, and the brain 
and spinal cord were congested. Other than this the animal appeared 
to be normal. 

TYPICAL CASE OP SHEEP NO. 201. 

Sheep No. 201, a ewe weighing 71 pounds, was brought into the 
corrals for feeding on August 16, 1913. On August 17, at 9 a. m., she 
was given 100 grams of ripe dry lupine seeds of Lwpinus leucopsis, the 
seed having been ground in a coffee miU and mixed with 100 grams 
of bran. At 9.30 a. m. this material had been eaten, and she was 
given 100 grams more of the ground lupine seed, mixed with bran as 
before. At 12.20 p. m. most of this material had been eaten. Her 
respiration was loud and deep, as in a sleeping animal. It was esti- 
mated that the animal had eaten altogether 175 grams of lupine seed, 
which would be the equivalent of 0.542 pound per 100 pounds of 
animal. 

On August 18, at 7 a. m., the animal appeared drowsy and sleepy. 
At 7.15 a. m. she walked about a little, throwing the forelegs out 
and dropping them as though lacking control. She staggered a 
little as she walked and appeared more sleepy than an hour earlier. 
There were some contractions of the surface muscles of the body. 
Plate II, figure 1, shows the condition of the animal at tliis time. At 
8.15 a. m. she was still upon her feet and able to walk aroimd, but 
walked as though tipsy. Wlien standing she appeared sleepy, the 
ears drooped, and the eyes were half closed. She stood with her legs 
bent at the knees and hocks. At 9.12 a. m. she stiU stood with the 



LUPINES AS POISONOUS PLANTS. 23 

same sleepy look and hanging ears, and occasionally walked about in 
an uneasy way. There was some lack of coordination of the muscles 
of the forelegs. Plate II, figure 2, shows the condition of the animal 
at that time, and Plate II, figure 3, shows tlie animal about 9.30 a. m. 
At 11.10 a. m. the condition was about the same as at 9.12. At 11.55 
a. m. the animal was found upon her knees; she got up with difficulty, 
but was barely able to stand upon her feet. She had been gradually 
growing easier, and at 12.10 p. m. was down with her head upon the 
ground, apparently in a sleep. At this time she was given 5 grams 
of tannic acid in water, and 5 minutes later 10 c.c. of gin was given 
in an ounce of water. At 12.20 p. m. she was found down in a corner 
of the corral \vith her head under her body. She was helped up, but 
feU down again on her side in a convulsive spasm. At 12.25 p. m. 
she lay quiet; her respiration was 32, deep and labored, and her pulse 
98, strong and regidar. At 12.30 p. m. an attempt was made to get 
her upon her ])eUy, but she roUed over on the other side. This was 
repeated several times. After several attempts she lay upon her 
belly with her nose extended on the ground. At 12.38 p. m. she 
tried to get upon her feet, but w'as unable to do so and went over 
on her side. Her legs straightened out, her head was thrown back 
in a stryclminlike spasm, respiration stopped, the eyes rolled back, 
and at 12.41 p. m. the animal was dead. 

At the autopsy a few petechige were found on the walls of the 
ventricles of the heart. The vessels of the small intestines were 
injected, and the brain was slightly congested. Nothing else abnor- 
mal was noticed. 

TYPICAI. CASE OF SHEEP NO. 253. 

Sheep No. 253, a ewe weighing 62.5 pounds, was kept in tlie corrals 
August 5, 1914, for feechng. 

On August 6, at 9.20 a. m., her temperature was 102° F., her pulse 
60, and her respiration 16. From 9.30 a. m. to 10.05 a, m. she was 
fed with the balling gun 195.31 grams of seed pods of Lupinus 
leucopsis. The pods were collected July 16, before the seeds had 
ripened, and allowed to dry. In the process of drying the seeds were 
expelled. The pods were ground and 4 ounces of water was added to 
facihtate the feeding. This was fed in the ratio of 312 grams of pods 
to 100 pounds of animal, ^yiowing for the loss of weight in the pods 
due to di'ving, this animal received an equivalent of 2.755 pounds of 
fresh pods per 100 pounds of animal weight. The sheep appeared 
all right during the day and was watched until 11p.m. 

On August 7, at 5.50 a. m., her temperature was 100.6° F., her 
pulse was 96, and her respiration 21. The animal "was found lying 
down with her head through the fence between the boards and swing- 
ing it from side to side. Her eyes were staring and expressionless. 
The femoral pulse was almost imperceptible. There was no evidence 



24 BULLETIN 405, U. S. DEPARTMENT OF AGKICULTUEE. 

of dyspnoea. At 6.35 a. m. she was still lying upon her belly, with 
her head through the fence and swinging it from side to side. She 
was taken up and put upon her feet and walked a little distance, 
staggering as she walked. At 6.40 a. m. her pulse was 140, the heart 
beating very hard. Her temperature was 100.6° F. and her respi- 
ration 24. The animal was standing with her head lowered and 
swinging from side to side. She staggered across the pen, hit her 
head against the fence, and pushed forward, with her head partly 
tmsted and under her body. As she lay down her head kept swinging 
from side to side. At 8 a. m. she was able to walk, but staggered as 
she moved. Her head was still swinging, pendulum fashion, from 
side to side. She pushed up against the side of the pen, preferably 
in a corner, with her head flexed toward the breast, so that at times 
she almost stood upon her head. 

Plate III, figures 1 and 2, taken at 7.55 a. m. and 8 a. m., respec- 
tively, show the positions assumed. At 8.55 a. m. the sheep was 
lying quietly at the front of the pen. Her respiration was 80. She 
no longer swung her head from side to side and did not attempt to 
push it against the side of the pen. At 9 a. m. her temperature was 
102;6° F., her pulse 102, and her respiration 86. The pulse was 
rather weak. There was some dyspnoea. She lay on her belly with 
her head to the left side and was quiet. At 9.15 a. m. she was up and 
about the corral. She would butt against the fence, then fall, 
extend the legs rigidly, and breathe rapidly. There was no rhythmic 
motion of the head at this time. At 9.40 a. m. she lay panting, with 
some frothing at the mouth. At 9.55 a. m. her pulse was 132, and 
strong in the femoral artery. Her respiration was 200, panting; her 
temperature was 103.2° F. She got her head into the corner of the 
corral and shoved forward until she almost stood upon her head. 
She struggled to push herself into this position, and as she was 
standing upon boards during the struggle her feet would sometimes 
slip and she would fall. After falling she would get up and start the 
butting process over again. At 10.35 a. m. she lay with her head 
to one side, the respiration being very rapid. She was disturbed, 
got up and started butting against the fence as before. This was kept 
up for two or three minutes, then she went down and remained lying 
mth her head on one side. Plate IV, figure 1, shows her position at 
10.40 a. m. At 10.55 a. m. the animal was up again and butting into 
the corners as before. She was drenched with 30 c. c. of whisky and 
an equal quantity of water. Her pulse was 132 and strong. At 
11.55 a. m. she stood with her head low and part of the time on one 
side. Plate IV, figure 2, shows her in this position. There was a 
rapid chewing motion of the jaws; the motion was dorsi ventral and 
not lateral. She bumped her head into the fence as before and 



Bui. 405, U. S. Dept. of Agriculture. 




Fig. 1.— Sheep No. 184 at 7.15 a. m., August 18, 1913. 




Fig. 2.— Sheep No. 184 at 8.57 a. m., August 18, 1913. 



Bui. 405, U. S. Dept. of Agncolture. 



Plate II. 




-Sheep No. 201 at 9.30 a. m 



Bui. 405, U. S. Dcpt. of Agriculture. 



Plate III. 




Fig. 1. -Sheep No. 253 at 7,55 a. m., August 7, 1914. 



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Fig. 2.— Sheep No. 253 at 8.00 a. m., August 7, 1914. 



j|. 405, U, S. Dept. of Airriculture 



Plate IV. 




Fig. 1.— Sheep No. 253 at 10.40 a. m., August 7 1914. 




Fig. 2.-SHEEP No. 253 at 11.15 a. m., August 7, 1914. 



LUPINES AS POISONOUS PLANTS. 25 

staggerod when she attempted to walk. At 11.22 a. m. she stood 
swaying from side to side. At 11.45 a. m. she was lying upon her 
belly with her head on one side, her respiration being about 200. At 
11.50 a. m. she was up on her feet and commenced to butt into the 
fence again. She soon fell and lay panting. Her respiration was 
160. At 11.57 a. m.'she was lying upon one side and panting. At 
12 noon she suddenly got upon her feet and started butting the 
corners, but immediately fell over, holding hor head on one side. 
The chewing motions, as noted before, were marked. At 12.15 p. m. 
she got upon her feet, tried to run but foil over; she picked herseK 
up, however, and started to butt into the comers. At 12.17 p. m. 
she fell down and lay quietly. At 12.30 p. m. she was on her side 
struggling in an attack of dyspnoea. At this time she was bled by 
cutting the angular artery of the eye. At 12.35 p. m. her respiration 
was 160. At 12.40 p. m. the movements of the jaws and lips still 
continued. At 1.10 p. m. she was struggling and the muscles of the 
flanks were trembling. Her pulse was so fast that it was impossible 
to count it. Her temperature was 107.6° F. At 1.11 p. m. she had 
fallen over on her side and was moving her body about. At 1 . 13 p. m. 
her respiration was barely perceptible, and at 1.15 p. m. it stopped. 
The movements of respiration and of the heart stopped at about the 
same time. 

In the autopsy petechige were found upon the auricles of the heart. 
The lungs were congested. The walls of the ileum were injected, with 
some ecchymoses. The mesenteric blood vessels were injected. 

LABORATORY EXPERIMENTS WITH EXTRACTS OF LUPINE SEED UPON 

MICE. 

Preliminary experiments showed that mice are very susceptible to 
poisoning by extracts of lupine seed injected intraperitoneally. 
Accordingly, a few experiments were undertaken to determine by 
tliis method the relative toxicity of extracts of various parts of the 
lupine plant. Seeds, pods, and leaves of Lupinus leucopsis collected 
at Greycliflf, Mont., in the summers of 1913 and 1914 were used for 
these experiments. The following is a description of the method 
used in preparing the extracts : 

Material was taken from each part of the plant which it was desired to examine, 
and all the samples were ground in the same mill set to the same degree of fineness. 
They were all ground the same day and at approximately the same time. From each 
fonn of material a sample of 20 grams was taken, placed in a flask, and macerated 
with 150 c. c. of Prolius's solution for 48 hours. The maceration of the different 
samples examined was begun and ended at the same time. Ninety c. c. of Prolius's 
extract was then taken from each flask, filtered, and evaporated down spontaneously. 
The residue of each was then extracted with 1 per cent of HCl, using 3 portions. 
The solution was filtered off, neutralized with NaXX);,, and made up to 10 c. c, so 
that 1 c. c. of the solution was equivalent to 1.2 grams of the sample. 



26 



BULLETIN 405, U. S. DEPARTMENT OF AGEICULTUEE. 



These extracts were made by Mr. O. F. Black, chemical biologist 
in the Office of Drug-Plant and Poisonous-Plant Investigations, and 
were used in intraperitoneal injections upon mice. Table 2 gives 
the results. 

Table 2. — Relative toxicity to mire nf the various parts of Lupinus leucopsis. 



Animal. 


Part of plant. 


Extract 
used. 


Plant used. 




Mouse. 


AVeight. 


Weight. 


Per 25 
grams of 
animal. 


Result. 


No 27 


Grams. 
24 
26.5 

14 

26.5 

20 

19 

15.5 

19.8 

19 

24 

19 

22.5 

21 


Leaves 


C.c. 
1 
.75 

!l5 

:l5 

.15 
.25 
.3 
.35 
.2 
.15 
.2 
.25 


Grams. 
1.2 
.9 
.6 

.18 

'i 

.3 
.36 
.42 
.24 
.18 
.24 
.3 


Grams. 
1.25 
.833 
.64 
.322 
.565 
.375 
.237 
.482 
.457 
.552 
.25 
.237 
.266 
.357 


Death in 7 5 minutes 


No. 35 

No. 44 

No 47 


do 

do 

do 


Death in 9.5 minutes. 
Death in 26 minutes. 
Not sick. 


No.36 

No.37 


Pods (seed removed).. 

do 

.do 


Death in 4.5 minutes. 
Death in 6.5 minutes. 
Not sick. 


No.38 

No. 43 


Pods (seed shed) 

do 

.do 


Very sick; recovery. 
Sick; recovery. 


No. 39 

No. 40 

No. 41 

No. 42 


Seed (1914 collection).. 
do 

Seed (1913 collection).. 
do 


Death in 12.5 minutes. 
Sick; recovery. 
Not sick. 
Death in 14 minutes. 



Table 2 shows that the amount necessary to kill a mouse on the 
basis of the standard weight of 25 grams is approximately as follows: 

Grams. 

Leaves 0. 6 to 0. 64 

Pods (seed removed) 3 to .35 

Pods (seed shed) 5 

Seeds, collection of 1913 3 to .35 

Seeds, collection of 1914 25 

Inasmuch as it is known from other experiments that the toxic and 
lethal doses are practically the same, it is fair to assume that this 
table gives, approximately, not only the lethal dose but also the 
toxic dose. From Table 2 it appears that the seeds collected in 
1914 were slightly more toxic than those collected in the preceding 
year. Possibly a certain amount of the toxicity was lost in keeping. 
It appears also that the pods from which the seed had been shed 
were only about half as toxic as the seed. The pods from which the 
seed had been removed were considerably more toxic than the pods 
from which the seed had been shed, and the leaves were only about 
one-half to one-third as toxic as the seed. These figures do not con- 
form very closely to those obtained in the field experiments upon 
sheep, but perhaps as closely as could be expected under the differ- 
ent conditions of experimentation. An especially interesting feature 
of this experiment was the definite proof obtained by Mr. Black by 
analytical methods of the presence of the alkaloids in the leaves, 
with the consequent deduction, confirmed by actual experiments, 



LUPINES AS POISONOUS PLANTS. 



27 



that the leaves are toxic. Inasmuch as the field experiments upon 
sheep were inconclusive in regard to the toxicity of the leaves, this 
is an important addition to the knowledge of the subject. 

Tlie field experiments gave little information as to the relative 
toxicity of the different species of lupines. There was nothing to 
indicate any difference in the toxic effect of those used in the fee(Ung 
experiments. Accordingly, a few experiments were made on mice with 
extracts of the seed of the available species. Seeds of three Ameri- 
can species were used, and through- the kindness of Mr. Piper, of the 
United States Department of Agriculture, seeds were obtained of the 
three common European species, Lujnnus alhus, L. angustifolius, and 
L. lutcus. Extracts of these lupines were prepared by Mr. Black, usmg 
exactly the same method as that employed in the precedmg test of 
the seeds of L. leucopsis. A series of tests was made on mice by 
intraperitoneal injection of these extracts. Table 3 shows the re- 
sults. In this table, for purposes of comparison, the experiments 
with seeds in Table 1 are included. 

Table 3. — Comparative toxicity to mice of the seed of different species rf lupines. 



I>lan1. 


Animal. 


Amount used. 


Used per 2n prams 
of animal. 






Mouse. 


Weight. 


Extract. 


Plant. 


Extract. 


Plant. 




Lupinus leucopsis: 
1914 seed 


No. 39. 
No. 40. 
No. 41. 
No. 42. 
No. 49. 
No. 49. 
No. 50. 
No. 51. 
No. 52. 
No. 53. 

No. 54. 

No. 56. 

No. 57. 

No. 58. 
No. 59. 
No. 60. 


Orams. 
24 
19 

22.5 
21 
18.5 


C.c. 
0.20 
.15 
.20 
.25 
.15 
.5 
.26 
.5 
.2 
.25 

.15 

.25 
.16 

.25 

■M 


Grams. 
0.24 
.18 
.24 
.3 
.18 
.6 
,3 
.6 
.24 
.3 

.18 

.3 

.18 

.3 

.18 
.09 


C.c. 


Grams. 
0.25 
.237 
. 266 
.357 
.25 
.8 
.30 
.65 
.25 
.3 

.335 
.2075 

.35 
.168 
. 1185 


Death in 12J minutes 


1)0 




Sick; recovery. 
Not sicif . 


1913 seed 




Do 






Lupinus luteus 

Do 


0.2 
.7 
.3 
.54 
.21 
.26 

.14 


None. 

Sick; recovery. 
Symptoms. 
Death in 3 minutes. 


Do 


2i 
23 

23.5 
24 

27 

22.5 
21.5 

21.5 
26.75 
19 


Lupinus albus 

Do 


Lupinus angusti- 
folius. 
Do 


Death in 19 minutes. 
Symptoms. 

Death in 6J minutes. 
Symptoms. 


Lupinus leucophyl- 
lus: 
1913 seed 


Do 




Lupinus argenteus: 
1913 seed 




Do 






Do 





Symptoms. 








In regartl to mouse No. 49, it should be stated that inasmuch as the 
first injection of 0.15 c.c. of extract produced no results, a second in- 
jection of 0.5 c.c. was given shortly afterward. From the known facts 
in regard to lupine poisoning it is not to be presumed that there was 
any appreciable accumulative effect from the precedmg injection. 
Table 3 shows very clearly that by this method of experimentation 
Lupinus albus and L. angustifolius appear to be about equally toxic. 
L. luteus, however, is much less toxic, it being necessary to take prob- 
ably three or four times the quantity in order to produce results. It 



28 BULLETIN 405, U. S. DEPARTMENT OF AGEICULTURE. 

may be noted in passing that L. luteus is the species which is said to 
be responsible for the so-called ictrogenic poisoning which occurs in 
northern Germany. In regard to the American species, L. leucopsis 
and L. leucophyllus are about equally toxic and do not differ much 
from L. alius and L. angustifolius. L. argenteus appears to be much 
more toxic than the other American species examined. 

It should be noted that in these experiments on mice the animals 
died of respiratory paralysis, with marked dyspnoea, the heart some- 
times contmuing to beat as much as a minute after respiration had 
ceased. The work with extracts is of a preliminary character, and 
it is intended to prepare for future publication an extended study of 
the alkaloids and the effect of the extracts. 

PART III.— DISCUSSION AND GENERAL CONCLUSIONS. 

FAILURE TO POISON SHEEP IN 1910, 1911, AND 1912. 

In the early work of the field experiments it was assumed that the 
lupines were sufficiently toxic to poison animals in the course of ordi- 
nary feeding. It was thought that if the animals were confined and 
given little or nothing of other food material and were abundantly 
supplied with lupine, symptons would appear if the plants were toxic. 

There was little in American literature to indicate the probable 
dosage. Chesnut and Wilcox (1901, p. 108) state that 150 pods were 
fed to each of two sheep and both were fataUy poisoned. Accord- 
ingly, in 1910 the sheep used were confined in corrals and were fed all 
they would eat. One animal, sheep No. 102, between July 6 and 30, 
ate 128 pounds of lupine tops, including leaves, flowers, and fruit, and 
another, between August 25 and September 7, ate 55.5 pounds of 
seed-containing pods, with no iU effects other than a loss of weight. 
Sheep No, 105, which received the 55.5 pounds of pods and seeds, was 
given on some days as much as 8 pounds. 

The experience of 1911 was similar and with no more results. 
Although a large number of experiments were made in 1912, in only 
one case were there harmful results. This animal, sheep No. 180, 
was fed 0.85 pound of lupine seeds on September 15, and the next 
day it was found dead in the pasture. At that time, because of the 
large number of negative experiments, it was thought that the death 
of the animal must be due to some other cause than lupine poisoning. 
The more complete knowledge of the effect of lupine, brought out in 
the work of 1913 and 1914, makes it evident that this was a case of 
lupine poisoning. AU the other cases of 1912 were negative. 

In comparing the work of these years it will be noticed that in 
1913 the feeding of seeds was done in a single day, and in most cases 
the quantity fed was eaten in a short time. This was true of sheep 
No. 180 in 1912, which ate the given quantity within an hour. In 



LUPINES AS POISONOUS PLANTS. 29 

1914 the experiments were by forced feeding, so that the animal 
received the total quantity in a short period of time; while m 1910 
and 1911 some of the animals received large quantities, but the feed- 
ing was distributed over a long period. Although in some cases as 
much as 8 pounds was fed in a single day, this was eaten in a more 
or less leisurely way. 

In 1912 two sheep, Nos. 175 and 168, were drenched with the fruit, 
No. 175 receiving 1.435 pomids and No. 168 4.198 pounds, and 
showed no symptoms, although the 1914 experiments indicated that 
the toxic dose of fruit is about H pomids. Sheep No. 175, however, 
received its luphie in three doses, between 10.30 a. m. and 3.30 p. m.; 
it is possible that tliis animal might have been poisoned had it re- 
ceived the material in a single dose, as the quantity given was close 
to the toxic hniit. But sheep No. 168 received 4.198 pounds, be- 
tween two and tlu-ee times the toxic dose as detemimed m 1914; 
this material was given in six doses, between 8 a. m. and 7 p. m. It 
seems probable that the only reason this animal was not poisoned 
was because of tlie lenglli of time during which the material was 
given. 

It appears to be a fan* inference that the excretory apparatus of 
the sheep can take care of the toxic substance of the lupuie provided 
the quantity given at any one time does not reach the toxic hmit. 
It is hoped to carry on later detailed experiments to show just how 
this is done — experiments for which adequate facihties have not been 
available thus far. It is probable, liow^evor, that this excretory work 
is done largely by the kidneys, since prelimmary experiments with 
other toxic substances upon sheep indicate that the kidneys are 
very efFicient in the removal of some toxic substances. It has also 
been shown by othei*s that the lupine alkaloids are found in the 
urine. The failure to get results in the earher experiments was due 
to the fact that the sheep did not get at any time more than the 
oxcretoiy apparatus could remove before the toxic limit was reached. 

LUPINE NOT A CUMULATIVE POISON. 

The lupines as poisonous plants do not have a cumulative effect. 
This has an important bearing on range management of sheep, for 
it is evident that sheep may graze contmuously on lupines with no 
bad results, provided the toxic limit is not reached at any one time. 
Inasmuch as the toxic dose is a fairly large quantity, and sheep do 
not ordinarily show any special fondness for the lupines, well-fed 
animals are not likely to be poisoned by lupmes. It is only when, 
for some reason, they eat an unusuall\^ large quantity that losses 
occur. This is discussed in more detail under "Range conditions 
imder which sheep are poisoned" on page 39. 



30 BULLETIN 405, U. S. DEPARTMENT OF AGEICULTURE. 

TOXICITY OF DIFFERENT SPECIES OF LUPINE. 

The field experiments give little information as to any difference 
in toxicity between the species of lupines. While only one of the 
two species used in the experiments with horses produced effects, viz, 
Lupinus myrianthus, the feedings of L. comatus were not conducted 
under exactly the same conditions, the period of feeding bemg con- 
siderably longer than in the experiments in which poisoning was pro- 
duced by L. myrianthus. 

The probable reasons why sheep were not poisoned on Lupinus 
myrianthus and L. comatus are discussed on page 28. Nearly all the 
experiments at Greycliff were on L. leucopsis. The field experi- 
ments on L. argenteus and L. leucophyUus were so few that it is not 
safe to make any deductions. It seems probable that in the experi- 
ments of feeding the seed of L. argenteus, the dosage was just a little 
too small, even granted that the plant is equally toxic with L. 
leucopsis. 

The experiments with mice detailed on pages 25 to 28 indicate that 
the European species, Lupinus alius and L. angustifolius, are about 
equally toxic with L. leucopsis and L. leucophyUus, while L. luteus is 
much less toxic, the dosage probably being at least three times as 
great as that for the other species. Inasmuch as the experiments 
on mice were few in number, too much importance must not be at- 
tached to the results. They are interesting, however, as giving some 
indication of the probable comparative toxicity of the species ex- 
ammed. These experiments with mice give an indication of the 
probable toxicity of the leaves as compared with other parts of the 
plants. 

TOXICITY OF LUPINE LEAVES FOR SHEEP. 

Sheep No. 243 was an undoubted case of lupine poisoning. The 
symptoms were typical and it received only loaves. It was impos- 
sible, however, to verify this by other experiments. The other ani- 
mals (Nos. 295, 266, 256, 290, and 306, withZ. leucopsis, and Nos. 263 
and 307 with L. argenteus) were fed much more, in some cases more 
than tln-ee times as much, without any effect whatever. It should 
be added that while all animals upon the range apparently graze 
upon lupine with impunity, sometimes eating very large quantities, 
there are cases when it seems probable that lupine leaves must be 
toxic. For example, cases of undoubted lupine poisoning in the 
Absaroka National Forest, examined by Dr. Hadleigh Marsh in the 
summer of 1914, apparently did not have an opportunity to obtain 
enough of the seeds to cause the difficulty. If it could be assiuned 
that the leaves are sometimes toxic, these cases would be much more 
easily explained. Many similar cases of range poisoning have oc- 
curred where it was difficult to explain the loss except by assuming 



LUPINES AS POISOXOUS PLANTS. 



31 



that the lupine leaves are to.xic. Moreover, laborator}- work, con- 
ducted with the assistance of Mr. O. F. Black, shows clearly that there 
is a large quantity of the alkaloid in the loaves, although less than in 
the seed. 

A careful analysis of the cases of sheep fed with leaves offers no ex- 
planation for the difference in results, although many possible factors 
have been taken into consideration, such as difference in animals, cUffer- 
enco in methods of administration, seasonal change of toxicity, etc. 
All that can be said at this stage of the investigation is that while lupine 
leaves are not always injurious they are toxic, and under some condi- 
tions — conditions wliich can not now be defined — they cause illness 
and death. It is evident that no definite statement can be made as 
to the toxic and lethal dose of leaves for sheep. 



TOXICITY OF LUPINE SEED FOR SHEEP. 

Table 4 is a statement of the sheep poisoned by lupine seed in 
showing the quantity in each case which produced the result. 

T.\BLE 4. — Sheep poisoned by lupine seed in 1913. 



913, 



Feed and animal. 


Date fed. 


Pounds 
fed per 

100 pounds 
of animal. 


Result. 


Unground seed : 

No. 209 


Aug. 15 
Aug. 17 

Aug. 15 
Aug. 17 
Aug. 31 
Sept. 2 
Sept. 6 


0.561 
.705 

.268 
..542 
.441 
.245 
.439 


Sick: repoverv. 
Death. 

Sick: recovery. 
Death. 

Do. 
Sick; recovery. 

Do. 


No. 1S4 

Ground seed: 

No. 210 


No. 201 


No. 1S5 

No.212 


No.203 





Inasmuch as sheep No. 208 received 0.551 pounds of the unground 
seed without any toxic effect, it would appear that the dose received 
by sheep No. 209 (0.561 pound) with resulting illness, must have been 
very near the toxic limit. As the only sheep that died (sheep No. 184) 
received 0.705 pound, the lethal limit, so far as these experiments 
show, lies between 0.561 and 0.705 pound. 

When gi-ound seed was used, the dosage was much smaller, as 
would be expected. Sheep No. 212 was poisoned by 0.245 pound, 
and sheep No. 210 by 0.268 pound. Others were fed larger quantities 
without effect; for example, sheep No. 196 received 0.425 pound, and 
sheep No. 207, 0.423 pound, wliile several received 0.3 pound or 
more. Sheep No. 196, however, received its dose in 2 daj^s, whereas 
the others received theirs in a single day. It seems that sheep may be 
poisoned on as little as 0.25 pound or may receive as much as 0.423 
pound without effect. 



32 BULLETIN 405, U. S. DEPARTMENT OF AGRICULTURE. 

The two cases of death resulted from doses of 0.543 and 0.441 
pound. The general deduction from the experiments of 1913 on 
ground seed was that the toxic dose was between 0.25 and 0.5 pound, 
and the lethal dose about 0.5 pound, with the probability tliat in the 
average cases the lethal dose was somewhat more, perhaps nearly 0.6 
pound. 

It was considered that these experiments determined the dosage 
nearly enough for practical purposes, and in the experiments of 
administering ground seed in 1914, which were mainly with reference 
to the effect of antidotes, the dosage was intended to be heavy enough 
to produce serious illness, if not death. The general results showed 
that the estimate of dosage made in 1913 was approximately correct, 
and that the toxic dose is somewhat less than 0.5 pound, sometimes 
as low as 0.25 pound. 

TOXICITY OF LUPINE PODS FOR SHEEP. 

The number of experiments of feedmg lupine pods was not suffi- 
cient to determine the dosage with any exactness. Sheep No. 253 
died on August 6, 1914, from eating 2.755 pounds of pods. This 
material had been collected previously and dried, but the weight as 
given is the green weight, as the loss from evaporation was known. 
These were pods in which the seed was not yet ripe. 

Sheep No. 301 died on August 28, 1914, from eating 2.041 poujids 
of pods which were collected after they had shed most of their seed; 
a few seeds, however, remamed attached to the pods. The weight 
given is the dry weight, as there was no way of estimating the loss 
of water in drying. In all the other cases much smaller quantities 
were fed, and no intoxication resulted. It can only be said that the 
pods are distinctly toxic, but the dosage is much greater than of the 
seeds. 

It may be added in this connection that in 1913 a careful compu- 
tation was made of the relative weights of the seeds and pods in the 
fruit, and that, based on the result of this w^ork, the toxic dose of pods 
would be 3.4 pounds. Without much doubt the toxicity of the pods 
varies at different seasons and probably is much reduced in the dried 
pods remaining attached to the plants in the late summer and fall. 

TOXICITY OF LUPINE FRUIT FOR SHEEP. 

By "fruit" is understood the pods with the contamed seeds. A 
considerable number of experiments were made to determine the 
toxicity of the fruit as compared with the seed. Table 5 gives the 
results of these experiments. The term "Seed heads" means the 
fruits and the stems bearing them. In the cases listed under "Fruit, 
fully developed," the pods were picked from the stems. 

The last four feedings under "Fruit, fully developed" were of 
very poor, locoed animals; consequently, the dosage (as computed 



LUPINES AS POISONOUS PLANTS. 



33 



according to weight) woiJd be distinctly different from that com- 
puted for the same animals iji a normal, healthy condition. Tliis 
may possibly explain why in the cases of Nos. 251 and 280 the dosage, 
computed on the basis of a lOO-poimd animal, so much exceeds the 
letlud dose shown in the precedmg experiments. For example, 
sheep No. 280 weighed 99 pounds earlier in the season, wliile at the 
time of the experiment it weighed only 84 pounds. If the dosage of 
material given September 4 were computed on the assumption that 
the animal had its original weight, it would reduce the amoiuit given 
m the table to approximately the toxic or lethal dose of the preceduig 
animals, and as the margin between no symptoms and toxicity is so 
small this animal woidd not differ materially from the othere. 

Table 5. — Sheep given forced feedings of lupine fruit in 1914- 



Fped and animal. 


Date fed. 


Pounds fed 
per 100 

pounds of 
animal. 


Uasult. 


Friut, fully developed: 
No 292 


July 16 


0.882 
.441 
1.322 
1. 7ti4 
1.543 
1.433 
1.543 
1.433 
1.763 
1.543 
1.541 
1.761 
1.901 

1.033 


Not sick 


No 291 


Jidy 17 


Do 




July 18 


Do. 








No 238 


July 20 .. . 


Do 


No 269 


July 23 


Not sick 


No. 240 


July 24 


Svmpt()ni.s. 
Not sick. 






No 250 


July 25 . . 


Death 


No 231 


Aue 29 


Not sick 


No. 235 


Au|:3i::::::::;:: 


Do. 


No. 251 


Sept. 2 ...... 


Do. 


No 280 


Sept 4 


Do. 


Seed head.s, hilly developed: 

No. 255 


July 2^29 


Do. 









It is evident from Table 5 that approximately 1 \ pounds of fuUy 
developed fruit will produce symptoms or death in a 100-pound 
sheep — that is, it takes three times as much of the fruit to poison as 
of the seed. 

SYMPTOMS. 

Some of the sheep poisoned by lupine, froth at the mouth, but this 
is by no means a universal symptom. The most noticeable and 
significant symptom is the character of the breathing. In the milder 
cases the brea tiling is heavy and labored, subsiding into a condition 
of coma in which the animal may contume for a long time, snoring 
as though in a deep sleep. If able to stand, the animal may fall 
over in its sleep. In the more acute cases, there are severe attacks 
of dyspnoea, duruig which the animtil tlu-ows itself about violently 
in its attempts to breathe. During these attacks the tongue and 
mouth become cyanotic from the congested peripheral blood ves- 
sels. Sometimes in these attacks of dyspnoea the animal dies in 
convidsions in which the limbs are extended rigidly, much as when 
poisoned by strychnin. In other cases the condition of coma deep- 



34 



BULLETIlSr 405, V. S. DEPARTMENT OF AGEICULTURE. 




ens until the animal dies without a struggle. The convulsive attacks 
of dyspnoea, however, may he considered typical of lupine poisoning. 
Drooping of the ears is noticeable in the early stages of the poisoning. 
In many cases the poisoned animal is contmually pushing its head 
agamst surroundmg objects. In corral cases the sheep pushes 
agamst the fence, lowering its head so that sometimes the animal 
almost stands on its head. These attitudes are shown in Plate III, 
figures 1 and 2. If moved from one point it may immediately push 
up against the fence in another place, sometimes throwing its head 

f,y^, Aj^ _^^ through an openmg 

and remaining in that 
position. Sometimes 
the head wiU be 
swung rhythmically 
from side to side. 

Generally when 
sheep become af- 
fected on the range 
they run about in a 
frenzied way, butting 
into other animals and 
objects. Handling the 
animals under such 
conditions excites 
them to such an ex- 
tent as seriously to 
interfere with their 
chances of recovery. 
When attempts were 
made to administer 
remedies by drench- 
ing, it was found that 
the animals lost more 
by the increased ex- 
citement than they 
gained from the remedy. If the sheep does not die in the period of 
excitement, it staggers until it falls, then lies in a stupor, which in 
the fatal cases gradually grows deeper. 

The pulse and respiration are very high in the acute stages of the 
intoxication, but later are not very different from normal, except 
that the pulse rate is frequently increased just before death. 

The intoxication produces no effect on the temperature, but in long- 
continued cases the temperature gradually faUs, sometimes to be- 
tween 98° and 99° F. The curves (fig. 2) showing the changes in 





1 


T^ 






























/ 














































/?£ 


S/ 


^W 


y\7 


70. 


V 










































1 
































o 




■^ 








1 


, 




__ 




_ 




' 


' 






— 




' ' 








\ 




















1 








\ 












T£. 


-M, 


0£ 


yp/^ 


^TUA 


=5f- 










\ 
































\ 




— 













__ 














" 


~ 




" 






" 

















Fig. 2. — Curves showing the changes in pulse, respiration, and tem- 
perature of sheep No. 1S5. 



LITPJNES AS POISONOUS PLANTS. 35 

the rate of tlie pulse, respii-atioii, and temperature of sheep No. 185 
are fairly typical of the cliauges wliieh ordinarily take place. 

Associated w^ith the condition of excitement there is frequently 
more or less violent trembling. Nausea is not often exhibited. 
Bloating occurs in some cases, probably being more likely to occur 
when the sheep eat very largely of lupine leaves. 

Especially characteristic of lupine poisonmg are: (1) Excitement, 
leading to running about and butting into other objects; (2) con- 
vulsions, accompanj-ing the attacks of dyspnoea ; and (3) heavy breath- 
ing, sometimes accompanied by snoring. 

There is considerable variation in the length of time which elapses 
between the feeding of lupine and the incidence of s\Tiiptoms of poison- 
ing. In some cases symptoms appeared in 1 or 2 hours, while there 
were other cases m whicli nearly 24 houi-s passed before symptoms 
were noticed. It is evident that namination does not necessarily 
precede the symptoms; in fact, there was no evidence that rumination 
occurred in any of the experuuental sheep, althougli as they were not 
under constant observation it could not be said positively that rumi- 
nation never took place. 

It can be seen from the experuuental work tliat sheep upon the 
range, when poisoned by lupine, may not exhibit symptoms until 
they have left the source of their trouble far behind. 

In the autopsies, the peripheral blood vessels were found strongly 
congested. The left heart was usually strongly contracted, and upon 
the surface of the heart in most cases were petechia\ The lungs were 
congested, and sometimes the liver. Tlie blood vessels of the brain 
were somewhat congested, and generally the blood vessels of the inner 
waU of the ileum were more or less congested. 

The immediate cause of death is evidently respiratory paralysis. 
Death may follow very quickly after the first symptoms, or the ani- 
mals may live for 2 or 3 days. 

As noted in the description of the experiments of intraperitoneal 
injection of lupine extracts in mice, the animals died of respiratory 
paralysis, showing symptoms which were comparable with those ex- 
hibited by sheep. 

The preceding details of sjmptoms are those exhibited by sheep. 
The experiments with horses were so few that no complete picture 
can be given. The distinct symptoms noted were twitcliing of the 
surface muscles, constipation, duUness, and a tendency when walking 
to lift the fore feet high. 

Dr. A. D. Knowles, of Butte, Mont., has recently treated some 
interesting cases of lupme poisoning of horses. Dr. Knowles has 
made a very careful study of these cases and has done some experi- 
mental feeding, makuig autopsies and having microscopic prepara- 
tions made of the diseased organs. These horses exhibited symptoms 



36 BULLETIN 405, U. S. DEPARTMENT OF AGEICULTURE. 

comparable with the "ictrogenic" poisoning reported in Germany, 
especially noticeable being the atrophy of the liver accompanied by 
a yellowing of the connective tissues. 

While some American authors have distinguished between "acute" 
and "chronic" lupine poisoning, their statements appear to have 
been drawn from European sources, and Dr. Knowles has apparently 
been the first to note and record definitely cases which can be diag- 
nosed as instances of "lupinosis" or ictrogenic poisoning. The clear- 
cut evidence presented by Dr. Knowles seems conclusive and makes 
it probable that other similar cases will be found, although it does 
not seem likely that lupine causes large losses of horses in the ag- 
gregate. 

PATHOLOGY. 

Some typical pathological material from the autopsies was exam- 
ined by Dr. Formad, of the Bureau of Animal Industry. A large 
amount of material remains for examination, which may be made 
the subject of a future report. The general character of the pre- 
liminary report was confirmatory of the results of the macroscopic 
examination of the cases. 

There was fullness and congestion of the pulmonary capillaries. 

The hepatic cells showed the presence of a mild degree of cloudy 
swelling and some oedema. 

The kidneys showed a slight degree of cloudy swelling of the 
epithelium, and iji some cases fullness between the convoluted 
tubules of the cortex and overdistension of the capillaries of the 
medulla accompanied in places by outwandering of the leucocytes 
and diapedesis of the red-blood corpuscles, indicatmg a marked 
congestion. 

COMPARISON OF "LUPINOSIS" AND POISONING OF SHEEP BY 
AMERICAN LUPINES. 

The symptoms of lupinosis are described in detail by a number of 
European authors, e. g., Ziim (1879), Arnold and Schneidemuhl 
(1883), Roloff (1883). Summaries are given by Dammann (1902, p. 
340-341) and Hutyra and Marek (1913, p. 524-525). 

The characteristic symptoms are : 

(a) Loss of appetite. 

(6) Fever in the first stages of the disease. 

(c) Weakness. 

(d) Cerebral excitement; thrusting the head against a wall and into corners. 

(e) Gnashing of teeth. 

(/) Pain in hind part of body. 
(g) Diarrhea; ill-smelling excrement. 
(h) Sometimes bloody urine, containing bile and albumen. 

(i) Yellowing of conjunctiva and visible parts of mucous membranes in most cases, 
but not in all. 

0') In some cases swelling of ears, eyelids, lips, and nose. 



LUPINES AS POISONOUS PLANTS. 37 

(it) In autopsies there is seen a citron-yellow color of the body tissues, hemorrhaj^es 
in various parts of the body, especially in the mucous membranes of the alimentary 
canal, the peritoneum, omentum, mesentery, the epicardium and endocardium, 
frequently fullness of gall bladder, generally an acute yellow liver atrophy, while 
in other cases the whole picture presents an appearance of acute phosphorus poisoning. 

The German authors distmguish between acute and chronic 
cases, the symptoms bemg the same, but ui the latter the liver 
exhibits chronic interstitial hiflammation, leaduig to atrophy of the 
organ, this beuig accompanied by nephritis and enlargement of the 
spleen. 

It will be noticed that the laboratory results obtained by Sollmann 
and by Clawson and Black agree very well wdth the field experiments 
with sheep, but differ very distinctly from the symptoms of lupmosis. 
The fever and jaundice which are especially characteristic of lupi- 
nosis have never been observed in sheep in America, either in experi- 
mental feedmg or in poisoning upon the range. It must be con- 
cluded that ictrogen is not the cause of loss of sheep on the ranges of 
the United States, but that the poisonhig is due to the alkaloids in 
the lupmes. 

The symptoms ui the corral experiments and hi range cases are 
distinctly those of alkaloidal poisonhig. The question naturally 
arises as to the explanation of the difference between the poisonhig 
of animals as exliibited in Germany and m the United States. The 
luphies examhicd in Germany possess alkaloids which are similar to 
those found m the American lupines, if not identical with them, and 
yet few clear cases of alkaloidal poisonhig of domestic aninnds have 
been reported, while in America there has been no poisonhig from 
ictrogen. In the absence of any determination of what ictrogen 
really is or how it; is formed, only a hypothetical explanation can be 
given. If it is granted that ictrogen is the cause of luphiosis and if 
the opmion is accepted, wliich seems to be held by the later authors, 
that ictrogen is formed by the action of microorganisms upon the 
lupme, a possible explanation lies hi the different conditions of the 
countries. The European lupines are cultivated plants, grown and 
handled like hay. The poisoning cases are caused by lupme that is 
exposed in the mass, and sometimes under conditions favorable to 
the growth of microorganisms. The American lupines are wdd 
plants, which grow in a somewhat scattered manner; they are not 
collected hi masses, and consequently do not have an especially 
favorable environment for the growth of microorganisms. More- 
over, it is very possible that the particular organisms which produce 
the toxic substance in Europe are not present hi this country; of 
this notliing can be said positively, for no one has yet been able to 
demonstrate that any specific organism or group of organisms is 
responsible for the hypothetical substance ictrogen. Therefore, on 
the supposition that there is such a substance as ictrogen, or lupino- 



38 BULLETIN 405, U. S. DEPARTMENT OF AGEICULTURE. 

toxin, it seems possible that it would not be produced in America, 
at least under range conditions. 

The fact that there is so httle evidence that domestic animals in 
Europe suffer from the alkaloids of lupine may be explained by the 
different way in which the animals are handled. It is shown else- 
where in this paper that lupine poisoning of sheep on the western 
ranges is ordinarily associated with deficiency in the food supply. 
Rarely, if ever, are well-fed sheep poisoned. It may be assumed 
that the sheep in Germany that feed upon the lupine are staU-fed or 
pasture-fed and eat somewhat at leisure, so that seldom would they 
be Ukely to reach the toxic limit in a single feeding. In this connec- 
tion, however, it may be noted that some of the symptoms men- 
tioned by the German authors resemble those of alkaloidal poisoning, 
and, granted that ictrogen is the principal cause of the losses, it is 
possible that there is a certain amount of alkaloidal poisoning in 
addition. This would account for the nervous symptoms described 
by the German authors, for these correspond to the phenomena 
exhibited by western sheep suffering from the lupine alkaloids. 

It should be noted in this connection that the work of Dr. Knowles 
mentioned on page 35 seems to show that under some conditions 
ictrogenic poisoning of horses may occur in America. 

The exact relationship between poisoning by lupine alkaloids and 
ictrogenic poisoning is far from clear, and it is to be expected that the 
chemical investigations which are now being carried on by the United 
States Department of Agricidture will aid in clearing up this subject. 

REMEDIES. 

It was hoped that some remedy might be found by which recovery 
from lupine poisoning might be aided, but the results of the experi- 
mental work in this direction were disappointing. Whisky, gin, and 
atropin were tried, with no beneficial results. Caffein and Epsom 
salts were used to increase excretion, but without any advantage. 
Tannic acid and sodium bicarbonate were used as antidotes. In the 
publication on Zygadenus,^ there is a discussion of reasons why the 
use of antidotes in a drench in any ordinary method of administra- 
tion should not be expected to be beneficial. As in the work on 
Zygadenus, experiments were made of giving sodium bicarbonate in 
frequently repeated doses. This was tried in four cases (sheep Nos. 
297, 254, 296, and 269). Sheep No. 269 received 0.772 pound of 
seed and died in spite of the remedy, but sheep No. 296 received 
0.666 pound, considerably more than the toxic dose, and was not 
sick. This animal received the sodium bicarbonate every half hour, 
while sheep No. 269 received it at hour intervals. There seems to be 
little doubt, as in Zygadenus poisoning, that if the sodium bicarbonate 

1 U. S. Dept. of Agr. Bui. No. 125, p. 41. 



LUPINES AS POISONOUS PLANTS. 39 

can be administered at intervals frequent enough to (^atch the toxic 
principle as it enters the fourth stomach, recovery may bo aided. 
This is of considerable theoretical interest, and the method might 
be used in order to save an especially valuable animal, but, of course, 
range animals can not be treated in this way, for the herder may 
have a large number of sheep sick at the same time. It is not 
imusual for 200 or 300 cases to occur suddenly, and any remedy 
which involves the administration of more than one or two doses is 
useless. 

Herders frequently bleed sheep poisoned by lupine and claim good 
results. There seems no logical reason for this, however, and the 
experience of the WTitcrs at the field station leads them to consider 
bleeding as harmful rather than beneficial. 

RANGE CONDITIONS UNDER WHICH SHEEP ARE POISONED. 

It must be recognized that corral experiments, while superior to 
laboratory M'ork in unravehng the complex problems of plant poison- 
ing of domestic animals, do not cover tlio conditions of range poison- 
hig. It is sometimes very diflicult to decide to what extent the results 
of intensive corral feeding can bo used in the explanation of range 
phenomena. Laboratory and corral experimentation are, of course, 
essential in such a study, and may give, in fact do give, fundamental 
information. An intimate acquaintance with range conditions is, 
however, necessary for the practical elucidation of these problems. 
Such an acquaintance with range conditions is somewhat difficult for 
the scientific investigator to acquire. Sheep are grazed in locations 
situated at long distances from regidar avenues of travel or communi- 
cation, and they are also moving from place to place. Cases of 
poisoning are reported, perhai)s, some chiys after the trouble has 
occurred, and investigation at that time is likely to be useless. It is 
very difficult for the investigator so to locate himself as to be able to 
see these cases when they occur. These difliculties doubtless explain 
why there has been so little exact knowledge of the conditions sur- 
rounding the losses. There has been, moreover, no way of placing a 
correct valuation on the reports made by sheep herders and o^vners. 
The average sheep herder does not have a high order of inteffigence, 
and this has led to an miderestimate of the testimony of these men, 
for the fact has been overlooked that many of them are keen observers 
with a practical knowledge of conditions far superior to that of the 
average scientific investigator. The writers of this paper have had 
long and intimate acquaintance with the western stock ranges, but 
they have frequently been put to shame by the wonderful, almost 
instinctive, readiness with wliicli an experienced sheepman will 
unerringly recognize slight symptoms of disease in the members of 
his flocks. The writers were fortunate in being able to observe many 



40 BULLETIN 405, U. S. DEPARTMENT OP AGKICULTUKE. 

range cases, and the conditions under which poisoning may occur 
seem now quite clear. 

It was early recognized that lupine poisoning ordinarily occurs 
only when hungry sheep graze upon the plants. WeU-fed bands 
are rarely, if ever, poisoned. This statement, it may be said in 
passing, can be made general and covers practically aU poisonous 
plants. If sheep are taken from the cars and turned into a pasture 
abundantly supplied with lupine, disastrous results are Hkely to 
occur. In July, 1914, 400 sheep, out of a band of 4,000, were lost 
near Lakeview, Oreg. The matter was investigated by Mr. Norman 
G. Jacobson, of the Forest Service, who found that the sheep had 
been driven 34 miles in four days with a scarcity of forage. On 
July 25, after a day's drive of 10 miles, they were turned into a 10- 
acre pasture which, investigation showed, contained httle but sage- 
brush and lupines, and the lupines were in pod. The sheep, of course, 
ate the lupines and with resulting loss. Many losses have occurred 
in the fall when sheep are coming down from the mountain ranges 
and have been caught by snow. On such occasions the fall of snow 
may cover the grasses, but leave the lupines exposed. Hungry sheep 
coming upon such an area may eat enough of the lupines to produce 
poisonmg. In the faU of 1913 a sheep owner in Montana lost 300 
sheep in this way. 

An area in the Caribou National Forest was investigated where 
aimual losses have occurred. It was found that the sheep coming 
from the mountains pass through thick patches of lupine and eat 
it greedily. The fact that the lupines are in pod at the time of the 
drive makes the matter worse. In 191 1 , an especially disastrous year, 
one outfit lost 1,000 head in this locahty. 

And yet, in spite of these kno-v^Ti cases of severe loss, sheep some- 
times graze on lupine through a good part of the season and with no 
harm. Except as they are especially hungry sheep rarely, if ever, 
eat enough of the lupine to cause trouble. Poisoning is much more 
hkely to occur if sheep are hurried over a lupine area, for then in 
their eagerness and jealousy of each other they seize upon the lupines, 
which are more easily reached than the grasses. Generally speaking, 
it is much better to drift sheep over a lupine area than to drive them. 
It may be noted that sheep that are new to a locality are much more 
likely to eat too much of the lupine than those that are accustomed 
to the country. 

An attempt was made in 1912 to demonstrate in an experimental 
way that hungry sheep may be poisoned when they feed upon lupine. 
A bunch of 11 sheep were kept without food for 36 hours and then, 
durmg one day, were driven 12 to 15 miles with very little opportu- 
nity to eat. About 5 p. m. they were brought to a thick lupme patch 
and allowed to graze. They fed imtil about 8.30 p. m., when they 



LUPINES AS POISONOUS PLANTS. 41 

were bedded down. They were up and feeding again at 12.15 a. m. 
and were grazing most of the time until 6.30 a. m., with the excep- 
tion of the hour from 4 to 5. To the disappointment of the observ- 
ers none of the animals was poisoned. It was noticed, however, 
that while a good deal of lupine was eaten they did not take to it 
greedily and preferred the grass, which was in fair abundance. 

In tliinking over the experiment later, it seemed probable that the 
fact tliat the sheep were allowed to feed freely, combined \vith the 
abundance of grass, might explain the lack of results. It was there- 
fore decided to repeat the experiment vnth the difference that the 
sheep should not be allowed to feed freely upon a lupine patch, but 
sliould be kept moving back and forth, the idea being that in this 
way they might snatch at the lupine as the most promment plant. 
An experiment of this kmd was tried July 31, 1914. Thirty-six 
sheep were corralled at night and kept in until 2 p. m. the next day 
with no ft)od. At 2 p. m. they were driven about a mile to a lupine 
patch having an abundance of pods and seed. It proved to be an 
unfavorable time for such an experiment, for it was very hot and tlie 
sheep would not feed until about 7 p. m. They grazed until about 
8 p. m. and were kept on the move all this time. They were driven 
back to the corrals. The time of grazing was so short that it was 
assumed the experiment was a faUure, and tlie sheep were not ob- 
served duruig the night. The next morning sheep No. 241, which 
had been observed as one of tliose eating th(> most lupme, was found 
douTi, and a little later it died, the symptoms and autopsy mdicat- 
rng tliat it was, without doubt, a lupine victim. The outcome of tliis 
experiment was considered to be a confirmation of tlie general ex- 
planation of range poisoning as given before. 

TREATMENT OF RANGE ANIMALS TO AVOID POISONING. 

From what has been said of the conditions imder wliich range poi- 
soning occurs, it is evident that much of the loss can be prevented by 
proper management of the bands. 

Sheep should never be taken from the cars to a pasture having 
much lupine. It is cheaper to buy hay. After long drives witli 
insufficient forage avoid grazing grounds wliich are covered with 
lupine. If it is necessary to drive sheep over lupine patches, do not 
hurry them, but allow them to spread out and drift across. Special 
care should be taken in the faU, when the grass may be covered by a 
fall of snow. In the treatment of the flocks remember the general 
fact, which is applicable in regard to all poisonous plants, that well- 
fed sheep are not likely to eat injurious plants. Conditions under 
which sheep get ravenously hungry should, if possible, be avoided. 

Herders should recognize the fact that the pods and seeds are espe- 
cially poisonous and that, consequently, poisonuig is more likely to 



42 BULLETIN 405, U. S. DEPARTMENT OF AGRICULTURE. 

occur at the time when the plants are in fruit and in seasons when 
the fruit is most abundant. In very dry seasons frequently little 
fruit is matured, while a wet season, especially a wet spring, may 
cause a heavy production of fruit. 

SUMMARY. 

(1) Lupines have been cultivated and used from the time of the 
ancient Greeks and Romans, but their poisonous properties have been 
recognized only in very modern times. Heavy losses of domestic 
animals were reported in northern Germany in 1872 and the suc- 
ceeding years. 

(2) While chemists have shown the presence of poisonous alkaloids 
in the lupines, the losses in northern Germany have been considered 
by investigators as due not to the alkaloids but to a hypothetical 
substance known as ictrogen. 

(3) An investigation by Dr. Sollmann showed the presence of 
alkaloids in American lupines, and pointed to the probability that 
most, if not all, the poisoning of live stock in America was due to 
these alkaloids and not to ictrogen. 

(4) Extended field work has verified the conclusions of Sollmann 
and has shown that all aerial parts of the lupines examined are 
poisonous, the seeds being the most toxic, then in order the pods and 
leaves. This has been confirmed by preliminary experiments with 
extracts upon mice. 

(5) The toxic substance is excreted by the kidneys; the intoxica- 
tion is not cumulative, and animals may eat comparatively large 
quantities with no ill results, if the toxic limit is not reached at any 
one time. Inasmuch as the toxic and lethal limits are nearly the 
same, the prognosis for poisoned animals is not favorable. 

(6) There is no form of remedial treatment that can be used ad- 
vantageously for range animals. Poisoning in most cases can be 
avoided, even where the plant is abundant, by careful handling of 
the flocks, especial care being taken to see that hungry sheep are 
not grazed on fields where there is much lupme. 



LITERATURE CITED. 

Arnold, Carl, and Lemke, Carl. 

1881. Beitrair zur Klarstellung der Ursache dor Liipinose. In Deut. Ztschr. 

Thiermed., Bd. 7, Heft 4, p. 251-265. 

and Schxeidemuhl, Georg. 

1883. Vierter Beitrag zur Klarstellung der Ursache und des Wesene der Lupinose. 
In Jahresber. K. Thierarzneischule, Hannover, Ber. 15, 1882/83, p. 
108-116. 
Baumert, Georg. 

1886. Ueber den "Bitterstoff," das Ictrogen und Lupinotoxin der Lupinen. In 
Arch. Pharm., Bd. 224, Heft 2, p. 49-59. 
Bellini, Ranieri. 

1876. Deir avvelenamento prodotto dai pemi del lupine. In Riv. Sper. Fren. e 
Med. L^g., ann. 2, fasc. 5/6, p. 581-€27. 
Bergh, G. F. 

1904. Ueber die Alkaloide der perennierenden Lupine. In Arch. Pharm., Bd. 
242, Heft 6, p. 416-440, 1 pi. 
Beyer, Ad. 

1871. Ueber einige Bestandtheilo des gelben Lupinenaamen. In Landw. Vers. 
Stat., Bd. 14, p. 161-176. 

CaLLSEN, JiJROEN. 

1899. Uebor die Alkaloide der Samen von Lupinus angustifolius und von Lupinus 
perennis var. polyphyllus. In Arch. Pharm., Bd. 237, Heft 8, p. 566-595. 
Oassola. 

1834. Note eur la lupinine. (Abstract by Julia-Fontenelle, with note.) In Jour. 
Chim. M6(\. Pharm. et Tox., t. 10, p. 688-689. 

For Gorman translation see Ann. Pharm. [Liebig], Bd. 13, Heft 3, p. 
308-309, 1835. 
Chesnut, V. K. 

1899. Preliminary catalogue of plants poisonous to stock. In U. S. Dept. Agr., 
Bur. Anim. Indus., 15th Ann. Rpt., 1898, p. 387-420, fig. 38-69. 
and Wilcox, E. V. 

1901. Stock-poisoning plants of Montana. A preliminary report. U. S. Dept. 

Agr., Div. Bot. Bui. 26, 150 p., 36 pi. 

CORNEVIN, C. E. 

1893. Des Plantes V^n^neuses et des Empoisonnements qu' elles Det^rminent. 
524 p., illus. Paris. 
Dammann, Carl. 

1902. Die Gesundheitspflege der landwirtschaftlichen Haussaugetiere. Aufl. 3, 

873 p., 74 fig., 20 col. pi. Berlin. 
Davis, L. S. 

1897. Die Lupanine der weissen Lupine. In Arch. Pharm., Bd. 235, Heft 3, p. 

199-217. 
Gemma, A. M. 

1882. Studi Sperimentali e clinici suU' azione della lupinina amorfa impura. In 

Gaz. Med. Ital. Lomb., v. 42 (s. 8, t. 4), no. 14, p. 147-149. 

43 



44 BULLETIN 405, U. S, DEPARTMENT OF AGRICULTURE. 

HuTYRA, Ferencz, and Marek, Jozsef. 

1913. Special Pathology and Therapeutics of the Diseases of Domestic Animals. 

Authorized Amer. ed. from the 3d rev. German ed., J. R. Mohler and 
Adolph Eichhorn, editors, v. 2, 163 illus., 5 pi. Chicago. 
KuHN, Julius. 

1880. Die Schmarotzerpilze der Lupinenpflanze und die Bekampfung der Lupin- 
enkrankheit der Schafe. In Ber. Physiol. Lab. u. Vers. Anst. Landw. 
Inst. Halle, Heft 2, p. 115-128. 
Landerer. 

1852. Ueber den Bitterstoff aus Lupinus. In Neues Repert. Pharm., Bd. 1, 
Heft 10, p. 445-447. 

LlEBSCHER, G. 

1880. Beitrag zur Klarlegung der Frage nach den Ursachen der Lupinenkrankheit 
der Schafe. In Ber. Physiol. Lab. u. Vers. Anst. Landw. Inst. Halle, Heft 
2, p. 53-114. 

LoWENTHAL, JULIUS. 

1888. Ueber die physiologischen'und toxicologischen Eigenschaften der Lupinen- 
Alkaloide. 26 p., Konigsberg. Inaugural-Dissertation. 

MUENK, GUSTAV. 

1914. Beitrage ziu- Kenntnis der Bestandteile und Wirkungen der Lupinensamen. 

In Landw. Vers. Stat., Bd. 85, Heft 6, p. 293-416. 
Plinius Secundus, Caius. 

1856. The Natural History of Pliny. Tr . . . by . . . John Bostock and H. T. 
Riley, v. 4. London. 
Raimondi, C. 

1891. Sur les principes actifs et toxiques du lupin. In Arch. Ital. Biol., t. 15, 
fasc. 2, p. 246-253. 

ROLOFF, FRIEDRlfcH. 

1883. Ueber die Lupinose. In Arch. Wiss. u. Prakt. Thierheilk., Bd. 9, Heft 
h, V- 1-54. 
Schmidt, Ernst. 

1897. Ueber die Alkaloide der Lupinensamen. In Arch. Pharm., Bd. 235, Heft 3, 

p. 192-198. 
1904. Ueber die Lupinenalkaloide. In Arch, Pharm., Bd. 242, Heft 6, p. 409-415 
Slade, H. B. 

1903. Some conditions of stock poisoning in Idaho. Idaho Agr. Exp. Sta. Bui. 
37, p. 159-190, illus. 
Wilcox, E. V. 

1899. Lupines as plants poisonous to stock. In Mont. Agr. Exp. Sta. Bui. 22, p. 
37-45. Literature, p. 43-45. 

WiLLSTATTER, RiCHARD, and FOURNEAU, ErNEST. 

1902. Zur Kenntnis des Lupinins. In Arch. Pharm. , Bd. 240, Heft 4, p. 335-344. 

ZiJRN, F. A. 

1879. Massenerkrankung von Schafen durch den Genuss befallener Lupinen, In 
Vortr. Thieriirzte, S. 2, Heft 7, 29 p. (p. 251-277), 6 fig. 



PUBLICATIONS OF THE U. S. DEPARTMENT OF AGRICULTURE RELATING 
TO POISONOUS PLANTS. 

AVAILABLE FOR FBEE DISTRIBUTION BY THE DEPARTMENT. 

Zygadenus, or Death Camas. (Department Bulletin 125.) 

Larkspur Poisoning of Live Stock. (Department Bulletin 365.) 

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Prevention of Losses of Live Stock from Plant Poisoning. (Farmers' Bulletin 720.) 

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Results of Loco- Weed Investigations in the Field, Laboratory Work on Loco- Weed 

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Barium, a Cause of the Loco- Weed Disease. (Biu-eau of Plant Industry Bulletin 129.) 

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The Relation of Barium to the Loco- Weed Disease. (Bureau of Plant Industry Bul- 
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